Temperature-controlled discrete sample analyzer

ABSTRACT

There is disclosed an apparatus for controlling the temperature of discrete sample containers in analytical instrumentation. A conveyor containing discrete samples to be analyzed is located in a subcompartment within a larger enclosure. A fan is mounted in a first opening in the subcompartment to move air from the large enclosure into the subcompartment. A second opening in which a thermal energy transfer element is mounted allows the passage of the air over the thermal energy transfer element back into the larger enclosure. A temperature sensor contacts a sample container being measured to provide a control signal which is applied to a proportionally controlled power supply connected to the thermal energy transfer element.

Unite States Inventors Appl. No.

Filed Patented Assignee atent Robert A. Ray;

James C. Sternberg, both of Fullerton, Calif.

June 30, 1969 Oct. 26, 1971 Beckmau 1nstruments,lnc.

TEMPERATURE-CONTROLLED DISCRETE [56] References Cited UNITED STATESPATENTS 3,031,267 4/1962 Martin et a1. 23/253 A 3,359,973 12/1967Hoffman 195/127 Primary ExaminerAlvin E. Tanenholtz Attorneys-Paul R.Harder and Robert J. Steinmeyer ABSTRACT: There is disclosed anapparatus for controlling the temperature of discrete sample containersin analytical instrumentation. A conveyor containing discrete samples tobe analyzed is located in a subcompartment within a larger enclosure. Afan is mounted in a first opening in the subcompartment to move air fromthe large enclosure into the subcompartment. A second opening in which athermal energy transfer element is mounted allows the passage of the airover the thermal energy transfer element back into the larger enclosure.A temperature sensor contacts a sample container being measured toprovide a control signal which is applied to a proportionally controlledpower supply connected to the thermal energy transfer element.

PATENTEUUET 2s ISYI INVENTORS ROBERT A. RAY

JANE c. s

NERG

TEMPERATURE-CONTROLLED DTSCRETE SAMPLE ANALYZER The present inventionrelates to apparatus for maintaining a sample container at apredetermined temperature in a discrete sample analyzer and moreparticularly to apparatus for controlling the temperature of a samplecontainer in a measurement position within a measurement compartment ofa fluorescent energy analyzer. Fluorometric analysis requires a highlysensitive laboratory instrument to make rapid fluorescent analyses ofdiscrete samples. A number of fluorescence measurements are required tobe made at a constant, controlled temperature. Constant temperature is aparticular requirement in studies involving enzyme reactions wherereaction rates are a function of temperature. In the enzyme-catalyzedreactions a fluorescing substance is either formed or consumed in theenzyme reaction. Therefore, the amount of fluorescence a sample producesupon exposure to a radiating source, is a measure of the degree ofreaction that has taken place up to the time of the measurement. Thedesired quantity or parameter to be determined is the rate of thereaction. Therefore, it is desired to measure the rate of change offluorescence as a direct indication of the reaction rate. Since the rateof enzyme-catalyzed reactions is temperature sensitive, it is necessaryto control the temperature of the sample container to maintain aconstant temperature over the period used to determine the reactionrate.

Generally, all fluorescent materials are affected by temperaturefluctuations. in most materials the fluorescence is inverselyproportional to temperature. Therefore, an increase in temperatureresults in a decrease in fluorescence intensity.

To provide temperature control for high precision measurements, mostfluorometers are equipped with a temperature controlled samplecompartment. Since the illuminating lamp source generates a considerablyamount of heat, it has been the practice in some fluorometric analyzersto control the temperature of the sample compartment by controlling theremoval from the compartment of the heat generated by the lamp. ln suchanalyzers the sample compartment is equipped with a water circulationsystem enclosed in ajacket surrounding the measurement compartment. Byattaching tubing to an inlet and an outlet fitting, satisfactory coolingcan be achieved with the flowing of tap water. in order to obtain thehighest precision desired, the cooling system is recommended in allanalysis procedures.

The temperature control in other analyzers is obtained by controllingthe temperature of the water which flows through the jacket surroundingthe sample compartment. This temperature control method has been foundto be very cumbersome because of the need of water carrying hoses and anexternal temperature controlling device for the water, as well as theneed for excessive periodic maintenance and inspection of the waterfittings and jacket for the purposes of detecting leaks. In addition,even with the water jacket temperature control, very poor temperaturecontrol of the sample compartment is obtained. Therefore, the methodswhich have been used to control the temperature of a sample compartmentin fluorometric analyzers have not proved entirely satisfactory.

It is the object of the present invention to provide apparatus foraccurately controlling the temperature of a discrete sample in adiscrete sample analyzer.

A further object is to provide temperature control of a sample in adiscrete sample analyzer by controlling the temperature of the fluidmedium surrounding and moving by the sample containers.

A still further object of this invention is to control the temperatureof the discrete sample container by sensing the temperature of thecontainer directly.

Still another objective of the present invention is to control thetemperature of discrete sample containers in a sample conveyor byapparatus which precisely and accurately determines the temperature ofthe fluid medium surrounding and flowing by the sample containers, suchtemperature being controlled by a temperature sensor contacting adiscrete sample container in the measurement position.

A still further object is to provide a method of mixing and blending thefluid medium which has been subjected to the transfer of thermal energyprior to passing the fluid into the sample compartment and over andaround the discrete sample container thereby avoiding unwantedtemperature gradients.

Other features and objects of the present invention will be betterunderstood from a consideration of the following detailed descriptionwhen read in conjunction with the attached drawing which illustrates thetemperature control apparatus constructed in accordance with theteachings of the present invention as part of a discrete samplefluorometric analyzer.

Referring now to the drawing, a measurement compartment 5 is mountedwithin the enclosure 7, the enclosure 7 containing all the components ofa fluorometer. An opening 9 in the measurement compartment 5 has a fluidor air mover or fan 11 mounted therein and driven by any suitable means,such as a motor, not shown. Another opening 13 in the measurementcompartment 5 has a thermal energy transfer element 15 positionedtherein. The thennal energy transfer element 15 is connected to a sourceof power 17 which in turn is connected to a controlling temperaturesensor 19. Temperature sensor 19 contacts sample container 21 shown inposition I of the sample conveyor or sample tray 23. Sample tray 23 ismechanically linked to a sample position control knob 27. Also containedin measurement compartment 5 is a source and detector apparatus 25containing a fluorescent energy source lamp 29, a phosphor sleeve 31,filter elements 33, a reference solution or reference bar 35, lenses 37,filter 39, and a photomultiplier detector 41. The input ofsignal-processing electronics 43 is connected to detector 41. Connectedto the output of electronics 43 are display meter 45 and strip chartrecorder 47.

The operation of the temperature control apparatus illustrated in thedrawing is described in detail as follows. The measurement compartment 5is constructed to have walls and covers to confine and direct air orfluid moving therein. The air is moved by a fan ll mounted in opening 9.The air is moved from the opening 9 through an opening 13 and past thethermal energy transfer element 15 mounted therein. The flow of air isindicated by the arrows in the drawing. As the air is moved into opening9 and out of opening 13 in measurement compartment 5, the air passesover the thermal energy transfer element 15 thereby being changed intemperature. Although thermal energy transfer element 15 is illustratedin one exemplary embodiment in the drawing as a heater element, it couldbe a cooling element or a combination of a cooling and heating elementsuch as provided by a heat pump or thermoelectric device well known inthe art of temperature control. By providing heating and coolingcapability, a wide range of ambient temperatures can be accommodated.The air passing out of opening 13 and over thermal energy transferelement 15 flows out into the confines of the enclosure 7. Enclosure 7has walls and covers to substantially confine and deflect the moving aircontained therein. Therefore the air flowing out of opening 13 and overthermal energy transfer element 15 is substantially confined withinenclosure 7 as indicated by the arrows. Enclosure 7 may have openingstherein by which air from outside the enclosure may enter or leave.However, the openings are such that they do not disturb the substantialairflow within the enclosure 7 thereby allowing the air motion asindicated. As a result, the heated air flowing from heater 15 issubstantially mixed with the air in enclosure 7 so as to become moreuniform in temperature before reentering compartment 5. This feature ofthe invention eliminates the requirement of mixing bafiles to obtainuniform temperature.

The thermal energy transfer element 15 is controlled by the source ofpower 17 containing a power supply and electronics to control powerdelivered from the power supply to the thermal energy transfer element.Temperature sensor 19 provides the control signal for the source ofpower T7. In operation temperature sensor 19 physically contacts asample container 21 in a conveyor measurement position 1, therebymeasuring the temperature of the sample container and producing a signalrelated thereto to control the power delivered to the thermal energytransfer element 15. As a result of the air passing over thermal energytransfer element through the mixing confines of enclosure 7 and intoopening 9 as driven by fan 11, the air flows in and around the samplecontainers held by sample tray 23. As the air passes over samplecontainer 21, the sample container is changed in temperature until thesignal generated by temperature sensor 19 indicates the sample containerhas reached the correct temperature for measurement. By such operationthe temperature of a sample container can be controlled to a fewhundredths of a degree centigrade.

Once the sample container 21 has reached equilibrium temperature,indicated by the temperature sensor 19, the fluorometer is ready toperform a fluorescence measurement of the sample. An enzyme catalyst isadded to the contents of the sample container 21 in the measurementposition 1 and the rate of the reaction resulting therefrom is measuredby the fluorescence from the sample container generated in response to asource of illuminating energy provided by lamp 29. Lamp 29 alternatelyproduces radiation to sample container 21 and to a reference bar orsolution 35, alternately causing the sample in the sample container andthe reference to fluoresce producing fluorescent energy collected bylenses 37 and directed into photomultiplier 41 where an electricalsignal is produced in response thereto. Various wavelengths ofillumination may be produced by selecting various combinations of aphosphor sleeve 31 and filters 33. In addition various fluorescentenergy wavelengths may be selected by filter 39.

Since the reference and sample fluorescent energies are alternatelydirected into photomultiplier detector 41, a signal is produced bydetector 41 having a magnitude proportional to the ratio of thereference and sample fluorescent radiations. Such an instrument iscalled a ratio fluorometer. The electrical signal from photomultiplier41 is amplified and further processed to produce a direct current signalof magnitude directly proportional to the alternating signal produced bythe alternate direction of reference and sample fluorescent radiationinto detector 41. Since the rate of reaction is the desired parameter,the electronics 43 contains a means of differentiation such that thesignal displayed by the meter 45 and the strip chart recorder 47directly display the rate of reaction taking place within the samplecontainer 21.

Because of the temperature control provided, the temperature of thesample container and the sample contained therein are maintainedconstant at a predetermined point to provide fluorometric reaction ratemeasurement of such precision and accuracy heretofore unrealized.

Although thermal energy transfer element 15 can be a heat pump or athermoelectric device which can either heat or cool, it may be desirableto have element 15 as a heating element or a cooling element, but notboth, and to have a separate heating or cooling element (notillustrated) mounted adjacent to a wall of enclosure 7. Thisrelationship may provide further simplification in control, for example,by providing a heating element as element 15 and a separate uncontrolledcooling element mounted in enclosure 7. The uncontrolled cooling elementenables the temperature control point of the sample container to belowered below ambient temperature to provide a measurement capability ofreactions occurring at temperatures below ambient. The arrangement ofelements can be reversed, having element 15 as a temperature-controlledcooling element and the element in enclosure 7 as an uncontrolledheating element. Further, the element in enclosure 7 can be temperaturecontrolled either separately or jointly with element 15, therebyproviding a greater range and accuracy of temperature control of thesample container To advance the conveyor tray 23 for the next samplemeasurement, knob 27 is operated to cause the tray to move into thedashed line position. The knob is then turned to rotate the tray toplace another sample container in the sample measurement position. Thetray is then placed back into the operating position by knob 27 therebycausing the new sample container to be contacted by temperature sensor19.

It now should be apparent that the present invention provides atemperature control apparatus for controlling the temperature of adiscrete sample in a discrete sample analyzer. Although a particularconfiguration and arrangement has been discussed in connection with thespecific embodiment of the temperature control apparatus constructed inaccordance with the teachings of the present invention, otherarrangements and configurations may be utilized. Furthermore, it will beunderstood that although an exemplary embodiment of the presentinvention has been disclosed and discussed, other applications andmechanical arrangements are possible and that the embodiment disclosedmay be subjected to various changes, modifications and substitutionswithout necessarily departing from this invention.

What is claimed is:

1. A discrete sample analyzer having a temperature-controlledmeasurement compartment into which discrete samples are introduced formeasurement comprising:

enclosure means having walls to substantially confine and deflect amoving fluid contained therein;

measurement compartment means mounted within said enclosure means, saidmeasurement compartment having walls to confine and direct the fluidmoving therein, said walls having a first and second opening into saidenclosure means;

fluid mover means mounted in one of said openings to provide a flow offluid from said enclosure means into said measurement compartment;

thermal energy transfer means mounted in the other of said openings toprovide a change in temperature of the fluid passing from saidmeasurement compartment into said enclosure means;

sample conveyor means in said measurement compartment to providetransportation of discrete samples from a holding position into ameasurement position within said measurement compartment;

sample temperature sensor means mounted in said measurement compartmentto provide a signal related to the temperature of said discrete samples;and

control means connected between said thermal energy transfer means andsaid sample temperature sensor to provide power to said thermal energytransfer means in response to said sample temperature sensor signal.

2. The discrete sample analyzer defined in claim 1 wherein the fluid isairv 3. The discrete sample analyzer defined in claim 1 wherein thefluid mover is a motor-driven fan.

4. The discrete sample analyzer defined in claim 2 wherein thetemperature sensor means is a thermistor.

5. The discrete sample analyzer defined in claim 1 wherein the thermalenergy transfer means is a heating element.

6. The discrete sample analyzer define in claim 1 wherein the thermalenergy transfer means is a cooling element.

7. The discrete sample analyzer defined in claim 1 wherein the thermalenergy transfer means is a heat pump.

8. The discrete sample analyzer defined in claim 1 further comprising asecond uncontrolled thermal energy transfer means mounted in saidenclosure means for changing the ambient temperature of said enclosuremeans to permit a wide range of temperature control points of the samplecontainer.

2. The discrete sample analyzer defined in claim 1 wherein the fluid isair.
 3. The discrete sample analyzer defined in claim 1 wherein thefluid mover is a motor-driven fan.
 4. The discrete sample analyzerdefined in claim 2 wherein the temperature sensor means is a thermistor.5. The discrete sample analyzer defined in claim 1 wherein the thermalenergy transfer means is a heating element.
 6. The discrete sampleanalyzer defined in claim 1 wherein the thermal energy transfer means isa cooling element.
 7. The discrete sample analyzer defined in claim 1wherein the thermal energy transfer means is a heat pump.
 8. Thediscrete sample analyzer defined in claim 1 further comprising a seconduncontrolled thermal energy transfer means mounted in said enclosuremeans for changing the ambient temperature of said enclosure means topermit a wide range of temperature control points of the samplecontainer.